[[amino-(2-bromo-6-methylpyridin-3-yl)methylidene]amino] 3-nitro-4,5-bis(phenylmethoxy)benzoate | 1229623-05-5

• 分子结构分类: 有机化合物 - 苯类化合物 - 苯和取代衍生物
• 英文名称: [[amino-(2-bromo-6-methylpyridin-3-yl)methylidene]amino] 3-nitro-4,5-bis(phenylmethoxy)benzoate
• CAS: 1229623-05-5
• 化学式: C₂₈H₂₃BrN₄O₆
• 分子量: 591.418
• InChiKey: RTJYTYHEMVOYCH-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  5.9
• 重原子数：
  39
• 可旋转键数：
  10
• 环数：
  4.0
• sp3杂化的碳原子比例：
  0.11
• 拓扑面积：
  142
• 氢给体数：
  1
• 氢受体数：
  8

反应信息

• 作为反应物：
  描述：

  [[amino-(2-bromo-6-methylpyridin-3-yl)methylidene]amino] 3-nitro-4,5-bis(phenylmethoxy)benzoate 以 N,N-二甲基甲酰胺 为溶剂， 反应 3.0h， 以38%的产率得到5-(3,4-bis(benzyloxy)-5-nitrophenyl)-3-(2-bromo-6-methylpyridin-3-yl)-1,2,4-oxadiazole
  参考文献：
  名称：

  Discovery of a Long-Acting, Peripherally Selective Inhibitor of Catechol-O-methyltransferase

  摘要：

  Novel nitrocatechol-substituted heterocycles were designed and evaluated for their ability to inhibit catechol-O-methyltransferase (COMT). Replacement of the pyrazole core of the initial hit 4 with a 1,2,4-oxadiazole ring resulted in a series of compounds endowed with longer duration of COMT inhibition. Incorporation of a pyridine N-oxide residue at position 3 of the 1,2,4-oxadiazole ring led to analogue 37f, which was found to possess activity comparable to entacapone and lower toxicity in comparison to tolcapone. Lead structure 37f was systematically modified in order to improve selectivity and duration of COMT inhibition as well as to minimize toxicity. Oxadiazole 37d (2,5-dichloro-3-(5-(3,4-dihydroxy-5-nitrophenyl)-1,2,4-oxadiazol-3-yl)-4,6-dimethylpyridine 1-oxide (BIA 9-1067)) was identified as a long-acting, purely peripheral inhibitor, which is currently under clinical evaluation as an adjunct to L-Dopa therapy of Parkinson's disease.

  DOI：

  10.1021/jm1001524
• 作为产物：
  描述：

  2-bromo-6-methylnicotinamidoxime 、 3-硝基-4,5-二苄氧基苯甲酸 在 N,N'-羰基二咪唑 作用下， 以 N,N-二甲基甲酰胺 为溶剂， 反应 1.0h， 以76%的产率得到[[amino-(2-bromo-6-methylpyridin-3-yl)methylidene]amino] 3-nitro-4,5-bis(phenylmethoxy)benzoate
  参考文献：
  名称：

  Discovery of a Long-Acting, Peripherally Selective Inhibitor of Catechol-O-methyltransferase

  摘要：

  Novel nitrocatechol-substituted heterocycles were designed and evaluated for their ability to inhibit catechol-O-methyltransferase (COMT). Replacement of the pyrazole core of the initial hit 4 with a 1,2,4-oxadiazole ring resulted in a series of compounds endowed with longer duration of COMT inhibition. Incorporation of a pyridine N-oxide residue at position 3 of the 1,2,4-oxadiazole ring led to analogue 37f, which was found to possess activity comparable to entacapone and lower toxicity in comparison to tolcapone. Lead structure 37f was systematically modified in order to improve selectivity and duration of COMT inhibition as well as to minimize toxicity. Oxadiazole 37d (2,5-dichloro-3-(5-(3,4-dihydroxy-5-nitrophenyl)-1,2,4-oxadiazol-3-yl)-4,6-dimethylpyridine 1-oxide (BIA 9-1067)) was identified as a long-acting, purely peripheral inhibitor, which is currently under clinical evaluation as an adjunct to L-Dopa therapy of Parkinson's disease.

  DOI：

  10.1021/jm1001524